Multidimensional heuristic process for high-yield production of astaxanthin and fragrance molecules in Escherichia coli

Zhang, Congqiang; Seow, Vui Yin; Chen, Xixian; Too, Heng‐Phon

doi:10.1038/s41467-018-04211-x

Cited by 116 publications

(169 citation statements)

References 52 publications

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“…Ajikumar et al [22] established a multivariate modular metabolic engineering (MMME) approach, which segments metabolic pathways into modules regulated by distinct promoters, to enhance taxadiene (a taxol intermediate) production by ~ 15,000 fold in E. coli. Variations of this modularization strategy have been implemented in E. coli [23,24] and in S. cerevisiae [25,26].…”

Section: Introductionmentioning

confidence: 99%

A modular pathway engineering strategy for the high-level production of β-ionone in Yarrowia lipolytica

Yang

Lin

et al. 2020

Microb Cell Fact

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Background: The GRAS and oleaginous yeast Yarrowia lipolytica (Y. lipolytica) is an attractive cell factory for the production of chemicals and biofuels. The production of many natural products of commercial interest have been investigated in this cell factory by introducing heterologous biosynthetic pathways and by modifying the endogenous pathways. However, since natural products anabolism involves long pathways and complex regulation, re-channelling carbon into the product of target compounds is still a cumbersome work, and often resulting in low production performance. Results: In this work, the carotenogenic genes contained carB and bi-functional carRP from Mucor circinelloides and carotenoid cleavage dioxygenase 1 (CCD1) from Petunia hybrida were introduced to Y. lipolytica and led to the low production of β-ionone of 3.5 mg/L. To further improve the β-ionone synthesis, we implemented a modular engineering strategy for the construction and optimization of a biosynthetic pathway for the overproduction of β-ionone in Y. lipolytica. The strategy involved the enhancement of the cytosolic acetyl-CoA supply and the increase of MVA pathway flux, yielding a β-ionone titer of 358 mg/L in shake-flask fermentation and approximately 1 g/L (~ 280-fold higher than the baseline strain) in fed-batch fermentation. Conclusions: An efficient β-ionone producing GRAS Y. lipolytica platform was constructed by combining integrated overexpressed of heterologous and native genes. A modular engineering strategy involved the optimization pathway and fermentation condition was investigated in the engineered strain and the highest β-ionone titer reported to date by a cell factory was achieved. This effective strategy can be adapted to enhance the biosynthesis of other terpenoids in Y. lipolytica.

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Section: Introductionmentioning

confidence: 99%

A modular pathway engineering strategy for the high-level production of β-ionone in Yarrowia lipolytica

Yang

Lin

et al. 2020

Microb Cell Fact

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“…As a result, they were able to achieve about 9.97 mg/g DCW of astaxanthin [70]. By developing and using an efficient multidimensional heuristic process and colorimetric medium screening approach, our laboratory has achieved one of the best results of astaxanthin using E. coli, 320 mg/L and 15 mg/g DCW [71]. As summarized in Table 2, the engineered S. cerevisiae [69], Y. lipolytica [66], Kluyveromyces marxianus [70] and E. coli [71] have produced promisingly high titers and yields of astaxanthin.…”

Section: Progress In Carotenoid Researchmentioning

confidence: 98%

Biosynthesis of Carotenoids and Apocarotenoids by Microorganisms and Their Industrial Potential

Zhang¹

2018

Progress in Carotenoid Research

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Carotenoids are a large group of natural pigments, ranging from red, to orange, to yellow colors. Synthesized by plants and some microorganisms (e.g., microalgae, fungi and bacteria), carotenoids have important physiological functions (e.g., light harvesting). Apocarotenoids are carotenoid-derived compounds and play important roles in various biological activities (e.g., plant hormones). Many carotenoids and apocarotenoids have high economic value in feed, food, supplements, cosmetics and pharmaceutical industries. Despite high commercial values, they are severely undersupplied because of low abundance in natural hosts (usually a few milligrams per kilogram of raw materials). Furthermore, plants or microbes usually produce mixtures of these molecules with very similar physical and chemical properties (such as α-and β-carotenes). All these features render the extraction from natural hosts rather difficult and also very costly both from process economics and sustainable land-use viewpoints. Chemical synthesis is also expensive due to structural complexity (e.g., astaxanthin has many unsaturated bonds and two chiral regions). Biotechnology via the rapidly advancing metabolic engineering and synthetic biology approaches has led to alternative ways to attain several carotenoids and apocarotenoids at relatively high titers and yields using fast-growing microorganisms. This chapter briefly reviews the biosynthesis of carotenoids and apocarotenoids by microorganisms and their industrial potential.

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“…Keasling's group tuned the expression of multiple genes within operons by generating libraries of tunable intergenic regions and balancing the expression of MVA pathway, which resulted in a 7-fold increase in mevalonate production (Pfleger et al, 2006). Zhang et al (2018b) reported a multidimensional heuristic process for astaxanthin production. Astaxanthin biosynthesis pathway was grouped into four modules, that each module controlled by different promoter of pre-determined strength, and get a yield of 320 mg/L in E. coli.…”

Section: Genetic Circuits and Dynamic Controlmentioning

confidence: 99%

Production of Terpenoids by Synthetic Biology Approaches

Zhang

Hong

2020

Front. Bioeng. Biotechnol.

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Terpenoids are a large family of natural products with remarkable diverse biological functions, and have a wide range of applications as pharmaceuticals, flavors, pigments, and biofuels. Synthetic biology is presenting possibilities for sustainable and efficient production of high value-added terpenoids in engineered microbial cell factories, using Escherichia coli and Saccharomyces cerevisiae which are identified as well-known industrial workhorses. They also provide a promising alternative to produce non-native terpenes on account of available genetic tools in metabolic engineering and genome editing. In this review, we summarize the recent development in terpenoids production by synthetic biology approaches.

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Multidimensional heuristic process for high-yield production of astaxanthin and fragrance molecules in Escherichia coli

Cited by 116 publications

References 52 publications

A modular pathway engineering strategy for the high-level production of β-ionone in Yarrowia lipolytica

A modular pathway engineering strategy for the high-level production of β-ionone in Yarrowia lipolytica

Biosynthesis of Carotenoids and Apocarotenoids by Microorganisms and Their Industrial Potential

Production of Terpenoids by Synthetic Biology Approaches

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